Enteric fever is a major problem for the developing countries because of poor sanitation and hygiene among people living here. Enteric fever or Typhoid fever is caused by the group of bacteria called Salmonella. This includes the Salmonella typhi and paratyphi strains.

Salmonella 

Salmonellae is a group of gram negative bacteria under the enterobacteriacae family. It posses three clinically important antigens:

Somatic Antigen (O Ag): This antigen is a part of the LPS cell wall of the bacteria. Used in WIDAL test and indicates recent infection as the antigen appears early and disappears early.

Flagellar antigen (H Ag): Made up of flagellar protein called “flagellin”, this confers motility to the bacteria. H antigen helps in identifying and differentiating between S. typhi, paratyphi A & B.

Surface envelope antigen (Vi Ag): it is a part of the capsule or the surface envelope protein, it is poorly immunogenic. It is used for making vaccines.

Pathogenesis

Salmonella typhi and Salmonella paratyphi A, B and C are responsible for causing enteric fever. The S. paratyphi C strain is not found in India. They are transmitted by the feco-oral route from human to human. Low socioeconomic status accompanied by poor sanitation and hygiene leads to the perfect recipe for rapid transmission of the bacteria among the population in developing countries.

Risk factors:

Decreased stomach acidity due to drug intake or H. pylori infection.

Prior GIT surgery.

Poor sanitation and hygiene.


Let’s now follow the bacteria through its journey in our bodies:

Bacteria is taken inside our body through the oral route when we eat food that is contaminated with Salmonella typhi and paratyphi.

The intestines are the perfect place for the bacteria to gain entry into the body. They use the M cells present in the epithelium to transport themselves in the wall of the intestine. The bacteria uses a type III transport system to enter the cell and stays in the vacuole of M cells.

Macrophages ingest the vacuole containing the bacteria. 

Bacteria posses system such as PhoP/PhoQ to help them survive inside the macrophage. These systems modify the LPS and outer membrane of the bacteria to make it resistant to enzymatic degradation.

The macrophages containing Salmonella now help in a transient primary bacteraemia by spreading to blood stream by lymphatic from the intestines.

The macrophages then later transport the bacteria to the reticuloendothelial system (spleen, lymph nodes, payer’s patches etc.) and organs like liver, gall bladder, kidneys etc. This results in the spread of the bacteria across the body.

The clinical manifestations by the bacteria are result of both the endotoxins by the bacteria and the release of various cytokines by the inflammatory cells.


Clinical manifestions:

Fever: there is a characteristic step ladder type of fever noted in cases of typhoid fever. There is associated sometimes with chills, myalgia and headache.

Rose spots: these are salmon coloured, blanching and maculopapular rash seen on the chest and back regions in almost 30 to 40 % of cases.

Intestinal manifestations: Abdominal pain, nausea and vomiting are the earliest symptoms that indicate involvement of intestines. Later on, if untreated will progress to intestinal ulceration and perforation.

Ulcers have undermined edges and are commonly seen in the ilieum due to the involvement of the payer’s patches. This later progresses to perforation of the intestinal wall causing haemorrhage, peritonitis and septicaemia.

Neurological manifestions: In rare cases the CNS is also involved leading to a condition called as “coma vigil” or “muttering delirium”. The patient keeps talking and tries to grasp objects that do not exist.


Diagnosis of enteric fever:

Bacterial culture is the gold standard for diagnosis: produces jet black or fish eye colonies in the culture medium due to production of hydrogen sulphide (H2S).

Best specimen for culture is: Bone marrow aspirate> blood. 

As discussed earlier enteric fever is mainly diagnosed by WIDAL test which is a serology test for detecting O and H antigens of the bacteria. WIDAL test is more sensitive and specific only 2nd week onwards.


Third week onwards stool and urine samples are used for detecting the bacteria as well as antigens.

Rapid tests such as typhi dot, ELISA and PCR are also available for diagnosing enteric fever.

Carriers:

Carriers play a key role in maintaining the chain of transmission of the bacteria. Bacteria colonise the gall bladder and kidney and continue to shed them in stool and urine.

 Carriers are classified based on the duration which they shed bacteria:

Convalescent Carrier: from 3 weeks to 3 months.

Temporary carrier: 3 months to 1 year.

Chronic carrier: more than 

It’s never complete without the mention of Mary Mallon also called “Typhoid Mary” a chronic asymptomatic carrier who spread the disease to more than 50 people and resulting in the death of 3. She was a cook by profession and handled food without appropriate hygiene and care.

Treatment:

In suspected cases of typhoid fever, empirical treatment can be started with:

Ceftriaxone 1 to 2 g/day IV

Azithromycin 1g/day oral

Drug sensitive typhoid fever:

Ciprofloxacin 500mg/day oral or 400mg IV every 12 hours.

Azithromycin 1g/day oral

MDR typhoid fever:

Ceftriaxone 2g/day IV

Azithromycin 1g/day oral

Prevention:

Let’s remember the golden rule - “Prevention is always better than cure”. Typhoid fever is a easily preventable disease. Let’s see what a common man can do to prevent it:

  • Promote cleanliness and good sanitation in the surroundings
  • Personal hygiene and regular hand wash before consuming food.
  • Stop open defecation.
Vaccination is available for enteric fever and it offers short term protection against it. There are two vaccines available:
  • Parenteral Vi antigen vaccine: given IV or subcutaneously. Protection upto 2 years.
  • Typhoral vaccine: uses live attenuated typhi strain. Given as three doses every alternate day. Protection upto 4 years.

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